Ali
Nokhodchi
*ab,
Alireza
Homayouni
c,
Ruta
Araya
d,
Waseem
Kaialy
e,
Wasfy
Obeidat
f and
Kofi
Asare-Addo
g
aSchool of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK. E-mail: a.nokhodchi@sussex.ac.uk; Tel: +44 (0)1273 872811
bDrug Applied Research Center and Faculty of Pharmacy, Tabriz Medical Sciences University, Tabriz, Iran
cSchool of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
dChemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB, Kent, UK
eSchool of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, UK
fJordan University of Science and Technology, Irbid, Jordan
gDepartment of Pharmacy, University of Huddersfield, Huddersfield, HD1 3DH, UK
First published on 18th May 2015
Ibuprofen exhibits poor flow, poor compaction and dissolution behaviour, and it is prone to capping after ejection from the die. Therefore, the aim of the present research was to engineer ibuprofen crystals in the presence of two disintegrants (starch and sodium starch glycolate) in order to improve its flow, compactibility and dissolution behaviour simultaneously. To this end ibuprofen and different concentrations of disintegrant (0.25 to 10% w/w in case of starch and 0.25 to 7% w/w in case of sodium starch glycolate) were dissolved in ethanol and water respectively. The ibuprofen solution was then added to the aqueous solutions containing the different concentrations of disintegrant. Ibuprofen precipitated within 10 min and the crystals were separated and dried for further studies. The obtained crystals were characterized in terms of flow, density, tablet hardness, dissolution behaviour and solid state. The results showed most of engineered ibuprofen to have better flow with a high compactibility. The results also showed that an increase in the concentration of starch in the crystallization medium resulted in a reduction in the hardness of ibuprofen tablets, but this was not the case for ibuprofen samples engineered in the presence of sodium starch glycolate. It is interesting to note that although engineered ibuprofen showed superior dissolution as compared to untreated ibuprofen, the highest concentration of starch (10%) or sodium starch glycolate (7%) slowed down the release remarkably due to an increase in the viscosity of the dissolution medium around drug particles. Solid state analysis (FT-IR, XRPD and DSC) ruled out the presence of different polymorphic forms and also any interaction between these disintegrants and ibuprofen. In conclusion, the engineering of ibuprofen in the presence of disintegrant showed how properties such as flow, compaction and dissolution behaviour can be simultaneously manipulated to suit a desired application.
Ibuprofen, 2-(4-isobutylphenyl)-propionic acid is a widely used analgesic and antirheumatic drug. It is a drug which is well known to exhibit poor flow properties and poor compression ability due to its high cohesive and viscoelastic properties respectively. A great problem in manufacturing is its high tendency of sticking to the punches.11
Moreover ibuprofen is also known as a poor water soluble drug. It is classified as class II according to the Biopharmaceutics Classification System (BCS) which means that it has high intestinal permeability and low water solubility. Therefore, dissolution of ibuprofen in gastrointestinal tract is a rate limiting factor for oral absorption and as such increasing the dissolution rate could increase the oral bioavailability of this drug. On the other hand, rapid drug release is preferable, especially for analgesic drugs.
Apart from acting as a disintegrating agent, starch has been widely used as a binder and also as a diluent in oral solid dosage formulations.12,13 Sodium starch glycolate is mainly used as a modern super disintegrant in oral dosage forms.14 Swain et al. (2015) used sodium starch glycolate in oral dispersible tablets to enhance the dissolution of ibuprofen through faster disintegration of tablets but no attempt was made to change the crystal properties of the ibuprofen.15 In another study solid dispersions of ibuprofen with starch 1500 was designed through factorial design to enhance the dissolution rate of ibuprofen, but stability of solid dispersions might be an issue in solid dispersion formulation due to the presence of amorphous structure.16
Many attempts have been made in the past to improve the properties of ibuprofen using different crystallization techniques or additives.7,17–20 An improvement of the flow characteristics and the compressibility of drug crystals have been observed, but not of dissolution at the same time, which is what this study is aiming to do. Therefore the aim of this project is to use a non-toxic solvent in a simple crystallization technique in the presence of starch and sodium starch glycolate to improve flow, hardness and dissolution of ibuprofen tablets simultaneously with no significant interaction between ibuprofen and starch derivatives. This piece of work will open up a new window for the possibility of enhancing these three important parameters simultaneously.
Sample | Drug![]() ![]() |
Ibuprofena | Starchb (w/v) | Sodium starch glycolateb (w/v) | %disintegrant attachedc (theoretical %disintegrant) |
---|---|---|---|---|---|
a The amount of ibuprofen dissolved in 10 ml solvent was 3 g for all samples. b These are the percentages of disintegrants in 100 ml of the solution. c Values in parenthesis show the theoretical %w/w of disintegrant added to the crystallization medium. | |||||
Ib1 | 3![]() ![]() |
10 ml | — | — | — |
Ib2 | 3![]() ![]() |
10 ml | 0.25% | — | 0.8 (7.8) |
Ib3 | 3![]() ![]() |
10 ml | 1% | — | 12.2 (25) |
Ib4 | 3![]() ![]() |
10 ml | 5% | — | 42.9 (62.5) |
Ib5 | 3![]() ![]() |
10 ml | 10% | — | 70.25 (76.9) |
Ib6 | 3![]() ![]() |
10 ml | — | 0.25% | 7.9 (7.8) |
Ib7 | 3![]() ![]() |
10 ml | — | 1% | 16.7 (25) |
Ib8 | 3![]() ![]() |
10 ml | — | 5% | 18.9 (62.5) |
Ib9 | 3![]() ![]() |
10 ml | — | 7% | 33.29 (70) |
![]() | (1) |
![]() | (2) |
It has already been shown that the crystal habit of ibuprofen depends on crystallization conditions such as the type of solvent and the presence of additives.23–26 The common crystal form of ibuprofen (Fig. 1) appears as fine acicular crystals with high cohesion tendency (Fig. 1a), which is reflected in its obvious poor flow which is discussed later. Starch and sodium starch glycolate showed almost similar morphology (rounded shape with smooth surfaces, Fig. 1b and c respectively). When ibuprofen was crystallized in the absence of any disintegrant, a different morphology was obtained with the crystals having rough surfaces comprising of flat-shaped ibuprofen particles sticking together to make bigger particles (Fig. 1d). Similar flat-shaped particles for ibuprofen were also reported when ibuprofen was crystallized in the presence of 5% PEG 8000.23 The presence of starch in the crystallization medium showed similar surfaces to ibuprofen crystallized in the absence of disintegrant but with lots of starch particles adhered to ibuprofen surfaces particularly at high concentration of starch (Fig. 1f–h). The presence of sodium starch glycolate in the crystallization medium changed the surface of the obtained particles. The presence of sodium starch glycolate particles on particle surfaces are not clearly seen (Fig. 1i–l). It was observed that ibuprofen particles crystallized in the presence of 7% sodium starch glycolate (Fig. 1l) were fairly large with stiff surfaces.
Table 2 shows that the true density of crystallized ibuprofen in the presence of additives is higher than the true density of ibuprofen in the absence of additives. This is due to the presence of starch and sodium starch glycolate with higher true density in the samples as the true density of starch (1.48 g cm−3) and sodium starch glycolate (1.56 is g cm−3) is higher than the true density of ibuprofen (1.10 g cm−3) crystallized in the absence of disintegrants (see Tables 2 and 3).
Formulation | Powder properties | ||||
---|---|---|---|---|---|
True density (g cm−3) | Bulk density (g cm−3) | Tapped density (g cm−3) | Carr's index (%) | Hausner ratio | |
Pure Ib | 1.14 ± 0.05 | 0.22 ± 0.08 | 0.31 ± 0.04 | 29.7 ± 0.5 | 1.42 ± 0.09 |
Ib1 | 1.10 ± 0.06 | 0.46 ± 0.09 | 0.51 ± 0.05 | 9.8 ± 1.0 | 1.11 ± 0.10 |
Ib2 | 1.17 ± 0.05 | 0.46 ± 0.05 | 0.50 ± 0.06 | 8.0 ± 0.9 | 1.09 ± 0.09 |
Ib3 | 1.18 ± 0.09 | 0.43 ± 0.03 | 0.50 ± 0.02 | 14.0 ± 0.1 | 1.16 ± 0.04 |
Ib4 | 1.33 ± 0.08 | 0.38 ± 0.02 | 0.53 ± 0.02 | 28.3 ± 0.1 | 1.39 ± 0.04 |
Ib5 | 1.40 ± 0.07 | 0.38 ± 0.03 | 0.50 ± 0.03 | 24.0 ± 0.1 | 1.32 ± 0.03 |
Ib6 | 1.17 ± 0.05 | 0.43 ± 0.05 | 0.50 ± 0.01 | 14.0 ± 0.1 | 1.16 ± 0.02 |
Ib7 | 1.19 ± 0.09 | 0.43 ± 0.04 | 0.52 ± 0.05 | 17.3 ± 1.0 | 1.21 ± 0.11 |
Ib8 | 1.42 ± 0.02 | 0.40 ± 0.04 | 0.51 ± 0.06 | 21.6 ± 1.0 | 1.23 ± 0.10 |
Ib9 | 1.45 ± 0.04 | 0.36 ± 0.01 | 0.50 ± 0.02 | 28.0 ± 0.1 | 1.39 ± 0.03 |
Sample | Particle size (μm) | |||
---|---|---|---|---|
X 10% | X 50% | X 90% | Span (X90% − X10%)/X50% | |
Pure ibuprofen | 48.1 | 131.7 | 435.6 | 2.90 |
Ib1 | 35.4 | 134.5 | 504.7 | 3.49 |
Ib2 | 55.2 | 257.8 | 708.3 | 2.53 |
Ib3 | 40.6 | 196.3 | 443.7 | 2.05 |
Ib4 | 42.8 | 170.9 | 348.4 | 1.79 |
Ib5 | 25.8 | 138.0 | 337.1 | 2.25 |
Ib6 | 47.4 | 245.8 | 654.6 | 2.47 |
Ib7 | 27.9 | 121.5 | 379.2 | 1.82 |
Ib8 | 29.2 | 107.7 | 225.0 | 1.82 |
Ib9 | 30.9 | 113.5 | 237.9 | 3.49 |
Comparing the flowability (Carr's index value) of the various recrystallized samples (Table 2) showed that ibuprofen samples recrystallized in the presence of low concentration of disintegrants (starch 0.25% (Ib2) and 1% (Ib3), sodium starch glycolate 0.25% (Ib6) and 1% (Ib7)) had lower Carr's index compared to those samples crystallized in the presence of high concentration of disintegrants (5% above). These CI values are also less than the CI value of untreated ibuprofen (CI of 29.7%). Such a decrease in CI indicates that there were great improvements in flow and packing ability of the powder mass in comparison to the commercial ibuprofen powder. This could be due to the existence of less elongated particles compared to the untreated ibuprofen which is obvious from SEM micrographs (Fig. 1). The changes in flow should be discussed under the context of the effect of particle size and shape. The flow properties of dissimilar materials with the same particle size have been investigated using permeability and shear cell28 indicating particle shape might have significant effects on powder flow. Recently Fu et al.29 carried out an extensive study on the effect of particle shape and size on the flow behaviour of various lactose powders. They showed that two lactose samples with identical shapes (SpheroLac® 100 and InhaLac® 230) but different particle sizes showed different Carr's index values. The lowest Carr's index (better flowability) was for Spherolac 100 reflecting its more efficient particle packing when in a conditioned and low stress state, due to having larger particle size and lower cohesivity. They also showed that two lactose samples with similar particle size distribution but different particle shape (SpheroLac® 100 and FlowLac® 100) showed less efficient packing for Spherolac 100 due to its irregular shape as compared to FlowLac®. The shear properties of 8 different powders, which varied in particle size and shape using an annular shear cell was also reported.30 They showed that needle shaped particles exhibited high angle of internal friction leading to poor flow. The above information can be applied to the engineered ibuprofen samples as discussed in the manuscript. It is generally believed that the flowability of powders decreases as the shapes of particles become more irregular.30 It can be noted that generally as the amount of disintegrant in the samples increases flowability seems to decrease. For example when starch concentration was increased from 1% (Ib3) to 5% (Ib4) the Carr's index also increased from 14% to 28.3%. Similarly when sodium starch glycolate concentration increased from 1% (Ib7) to 5% (Ib8) CI increased from 17.3% to 21.6%. The results generally showed that high concentration of disintegrant is not in the favour of good flow for the engineered ibuprofen powder. The improved flowability observed from the results may also be due to the higher bulk densities observed for the modified ibuprofen samples (Table 2) being in the range of 0.36–0.46 g cm−3 compared to 0.22 g cm−3 for untreated ibuprofen. Recently Jallo et al.31 made an attempt to enhance the bulk density of pharmaceutical powders by dry coating to modify the surface of the particles in order to improve the flow. They showed that the coated particles showed higher bulk density and their flow moved from a poorer to a better flow classification. Ibuprofen engineered in the absence of any disintegrant also showed lower CI which is an indication of excellent flow which could be due to the rounded shape of these particles. Hausner ratio also confirmed a similar pattern where untreated ibuprofen showed the highest Hausner's ratio (1.42). According to Wells32 a Hausner ratio value of less than 1.20 is indicative of good flowability of the material, whereas a value of 1.5 or higher suggests a poor flow display by the material. It can be concluded that engineering ibuprofen particles in absence or presence of low concentration of disintegrant enhances the flow properties of ibuprofen powders.
Table 3 also shows that the presence of disintegrants in crystallization medium produced narrower particle distribution (smaller value of span indicates narrower particle size distribution). It has been investigated that fine particles having high surface to mass ratios are more cohesive than coarser particles, which results in inappropriate flow properties.35
![]() | ||
Fig. 3 Hardness–pressure profiles of various engineered ibuprofen tablets in presence of starch (A) and sodium starch glycolate (B). |
Generally, poor compactibility of powders could be due to a poor or lack of plastic deformation during compaction or lower elastic moduli of powders which is accompanied by high elastic recovery. When the pressure is removed the stored elastic energy is released which leads to a volume expansion of the particles and the tablet. This in turn can break (or weaken) the bonds between particles (at atomic distances) formed during the compaction process which leads to an increase in the porosity of tablets and reduction in the tablet hardness.36 The authors believe that in the present study at optimum compaction pressure, the tablets can retain their integrity much better (low tablet porosity) compared to the tablets compressed at high pressures. For example the porosity of tablets made from crystallized ibuprofen without any additives was 22.0 ± 1.2, 17.2 ± 2.1 and 20.0 ± 1.1% at compaction pressures of 35, 105 and 175 MPa respectively. This indicates that the maximum hardness was obtained when the porosity was the least. Similar patterns were observed for ibuprofen samples crystallized in the presence of 5 and 10% starch. The tablet porosities for 5% starch samples were 30.1 ± 1.0, 25.4 ± 1.4 and 35.5 ± 1.5% and for the 10% starch samples it was 37.1 ± 0.9, 32.0 ± 1.8 and 36.2 ± 2.1% at compaction pressures of 35, 105 and 175 MPa respectively. A similar conclusion was reported for caffeine tablets where the tensile strength of caffeine tablets compressed at low pressure was much higher than those tablets compressed at very high pressures.37 A reduction in the mechanical strength of tablets could be due to high elastic deformation which is a common sign of over-compaction. The reduced tablet hardness of some formulations in the present study suggest that the detrimental effect of porosity as a result of elastic recovery on tablet mechanical strength may have outplayed the bonding strength acquired due to elevated pressures. It has been reported that these alterations in hardness of tablets with compaction load changes could be due to changes in the elasticity of starch and sodium starch glycolate which changes the bonding between particles under compaction.38
Fig. 3 also showed that in most cases treated ibuprofen samples (with or without disintegrant) showed higher mechanical strength compared to untreated ibuprofen samples particularly in case of ibuprofen engineered without the presence of additives. But the presence of additives is essential to get improved dissolution which is discussed later in the dissolution section. In order to have a better visualization of the effect of concentration of disintegrant on hardness of ibuprofen tablets the concentration of disintegrant used in the crystallization medium versus hardness was plotted (Fig. 4). It can be seen from Fig. 4A that as the concentration of starch in the crystallization medium increases the hardness seems to decrease remarkably. The tablets made from the samples Ib4 and Ib5 (starch 5% and 10% w/v respectively) were very weak under any compaction pressure used in the present study (Fig. 4A) which might be due to poor bonding properties of starch which tends to increase capping leading to very poor mechanical strength particularly at high concentration of starch.39 This was not the case for ibuprofen samples crystallized in the presence of sodium starch glycolate. It has been reported that Na starch glycolate was successfully used in direct compaction formulations.40 It is obvious from SEM images in the cases of 5 and 10% starch that the surface of the ibuprofen crystals were covered mostly by starch particles and as such during the compaction process, bonding occurs only between starch particles (Fig. 1) which are weaker than the bonding between ibuprofen–starch particles. It has been reported that this bonding between starch–starch particles is weak which could be the main reason for the poor mechanical strength of tablets obtained for these two formulations when high concentration of starch was used.39
![]() | ||
Fig. 4 The effect of %disintegrant (starch (A) and sodium starch glycolate (B)) used in the crystallization medium on hardness of ibuprofen tablets. |
In case of sodium starch glycolate less sensitivity of the hardness of ibuprofen tablets against the concentration of sodium starch glycolate was observed (Fig. 4B). It was interesting to note that at high compaction pressures (140 and 175 MPa), higher concentration of sodium starch glycolate produced harder tablets. This might be due to the better compactibility of sodium starch glycolate in comparison with starch. The higher hardness values of the tablets are indicative of stronger interparticulate bonding between the agglomerates compared to the untreated crystals.
For a better comparison between untreated ibuprofen and treated ibuprofen in the presence of disintegrants, physical mixtures of ibuprofen–disintegrant which have identical composition to the treated samples were prepared (only 0.25 and 1% disintegrants were prepared as higher concentration of starch 5 and 10% gave tablets with very poor mechanical strength). The hardness values of the physical mixtures and treated ibuprofen–starch were shown in Fig. 5A. The results showed that in most cases treated samples in absence or presence of additives showed better mechanical strength compared to their counterpart physical mixtures. It has been reported that poor compactibility of drug crystals can be attributed to the presence of crystal faces that give poor adhesion to other crystals and the absence of the faces that are required for optimal adhesion.7 Here, for the ibuprofen crystals, the relative abundance of the different faces within the crystals was modified. This can affect the interparticulate bonding between these crystals, resulting in different compression properties.
![]() | ||
Fig. 5 Comparing hardness–pressure profiles between crystallized ibuprofen and their physical mixture counterparts (SSG = sodium starch glycolate; PM = physical mixture; Ibu = ibuprofen). |
It is known that there is a high affinity of the ibuprofen powder to stick to the tablet punches.11 The common crystals stick to the punches due to its high cohesivity. A sticking to the punches was not observed for ibuprofen that was crystallized in the presence of starch or sodium starch glycolate. This indicates that differences concerning the surface structure of the crystals occur during the employed crystallization process. Previous research has shown that adhesion of ibuprofen formulated with 29.5% lactose monohydrate (Tablettose®) to the tablet punches during tableting is influenced by the type of tooling used and the type and level of lubricant in the formulation.41 The adhesion of ibuprofen to the upper punch was determined by removing the upper punch and dissolving the powders stuck to the punch in ethanol after each compaction. The amount of ibuprofen in the solution was spectrophotometrically determined. Roberts et al.41 showed that all ibuprofen formulations adhered to the punches with the highest being around 8 μg mm−2, whereas this was not the case for the recrystallized ibuprofen in the absence and presence of starch derivatives used in the present study and there was no need to incorporate a direct compression filler such as Tablettose®. This may be accredited to a change in the interaction between the punch face and particle surface as a result of the different morphology obtained following recrystallization as compared to untreated ibuprofen.
![]() | ||
Fig. 6 Dissolution profiles of various crystallized ibuprofen from tablets made at 105 MPa compaction pressure ((A) samples containing starch and (B) samples containing sodium starch glycolate). |
Table 1 shows that in the case of sodium starch glycolate, more disintegrant attached to ibuprofen particles compared to starch when the ratio of ibuprofen:
disintegrant was 3
:
0.25 w/w (this formulations contained around 8% sodium starch glycolate) (Table 4) therefore faster dissolution was expected for this formulation (Fig. 6A). But, as more Na starch glycolate was incorporated, the dissolution rate became slower due to the formation of a very viscose gel around ibuprofen particles during the dissolution process making it difficult for the dissolution medium to penetrate into the tablet or granules thereby retarding the diffusion of the drug solution from the tablet to the dissolution medium. Similar findings were found and reported for methylprednisolone and phenylbutazone when high concentration of sodium starch glycolate was incorporated in their tableting formulations.44 For example at very high concentration of disintegrant (ibuprofen
:
disintegrant 3
:
7 w/w; contains 70% disintegrant) during the crystallization process around 33% Na starch glycolate will be associated with the ibuprofen particles which is high enough to make a viscose gel around the particles (see Tables 1 and 4).
Formulation | Peak (°C) | Enthalpy (J g−1) | %Ib (obtained from UV) |
---|---|---|---|
a Values are represented as mean SD, n = 3. | |||
Pure ibuprofen | 78.97 ± 0.23 | 119.8 ± 19.4 | 100 |
Ib1 | 77.59 ± 0.09 | 113.9 ± 1.6 | 99.4 ± 1.9 |
Ib2 | 77.63 ± 0.03 | 114.7 ± 0.5 | 99.2 ± 0.1 |
Ib3 | 77.57 ± 0.07 | 103.2 ± 1.5 | 87.8 ± 3.1 |
Ib4 | 77.12 ± 0.25 | 53.1 ± 0.1 | 57.1 ± 7.5 |
Ib5 | 76.35 ± 0.07 | 29.2 ± 3.3 | 29.8 ± 2.7 |
Ib6 | 77.59 ± 0.14 | 110.2 ± 2.3 | 92.1 ± 2.4 |
Ib7 | 77.66 ± 0.03 | 100.3 ± 2.2 | 83.3 ± 0.2 |
Ib8 | 77.76 ± 0.22 | 92.5 ± 0.2 | 81.1 ± 1.2 |
Ib9 | 77.85 ± 0.23 | 71.2 ± 1.8 | 66.6 ± 4.5 |
For better comparison of the dissolution performance of crystallized ibuprofen in the presence of disintegrants, further dissolution tests were carried out only on starch samples as this disintegrant is the most commonly used disintegrant and also it is very cheap. To this end two ratios of ibuprofen:
starch (3
:
0.25 and 3
:
1 w/w) were selected and their physical mixture counterparts were prepared (exactly the same composition as crystallized samples). Crystallized ibuprofen in the presence of starch (1% formulation) showed a remarkably faster dissolution as compared to its physical mixture counterpart (Fig. 6). Ibuprofen crystallized with a low concentration of starch (0.25%) did not show any significant difference with its physical mixture counterpart (Fig. 7).
Table 4 shows a slight reduction in the enthalpy of ibuprofen crystallized in the absence of disintegrant (Ib1) compared to untreated samples which could be due to differences in their particle sizes. These changes in DSC data may be an effect of crystal size (crystal habit) and the amount of disintegrant contained in the sample.6,45 A significant reduction in enthalpy of the treated samples in the presence of disintegrant is due to the presence of disintegrant in the samples. These enthalpies can be well correlated to the amount of disintegrant associated with the samples after crystallization (Table 4). A reduction in the enthalpy of crystals has been reported for other drugs as the presence of dissolved impurities (additives) may change the rate of crystallization and crystal habit by adsorbing the surface-active agents to the nuclei or growing crystals.46
The assay results presented in Table 4 show that the value of ibuprofen assay is higher than expected value. This indicates that during the crystallization process some of the disintegrants were lost leading to high contribution of ibuprofen in the samples.
![]() | ||
Fig. 9 FT-IR of some of crystallized ibuprofen samples and the excipients used in the crystallization medium (Ibu = ibuprofen; SSG = sodium starch glycolate). |
To confirm the above findings XRPD was carried out on all samples including pure ibuprofen and disintegrants used in the present study (Fig. 10). It has been reported that ibuprofen characteristics peaks are in 2θ of around 16, 20 and 22.47 These peaks are shown in Fig. 10 using black arrows. All XRPD shown (except pure starch and sodium starch glycolate) in Fig. 10a and b contained all these three diagnostic peaks showing the crystalline nature of the ibuprofen in these formulations. The smaller intensity of the samples crystallized in the presence of additives could be due to amorphous nature of starch and sodium starch glycolate associated with the ibuprofen. In case of ibuprofen crystallized in absence of additives the difference in the relative intensity of the peaks is due either to the variation of the crystal habit, because the relative abundance of the planes exposed to X-ray source is altered, or to differences in the size of the crystals.
![]() | ||
Fig. 10 XRPD of various ibuprofen crystallized in the presence and absence of starch (A) and sodium starch glycolate (B). |
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